Anxiety and Depression Are Related to Higher Activity of Sphingolipid Metabolizing Enzymes in the Rat Brain

Zoicas, Iulia; Mühle, Christiane; Schmidtner, Anna K.; Gulbins, Erich; Neumann, Inga D.; Kornhuber, Johannes

doi:10.3390/cells9051239

Cited by 18 publications

(10 citation statements)

References 51 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Altogether, these findings suggest that a bad long-term memory is associated with an enhanced depression-like state, but not with anxiety, which is possibly mediated by enhanced NC activity in the VM. Our results are in line with the previous data showing that the depression-like phenotype is associated with enhanced activities of NC and AC [10].…”

Section: Local Nc Activity and Emotional Statussupporting

confidence: 93%

“…The ceramide rheostat is a crucial mechanism of cell membrane integrity determining synaptic appearance and signaling [40]. High abundance of ceramides, their precursors and metabolites in the brain [41] determines the specific involvement of these molecules in the pathogenesis of several psychiatric disorders [2,7,[9][10][11][12][13][14][15][16][17][18][19][20]. Recent data show that the ceramide system also contributes to the mechanisms of memory performance both under physiological conditions [26][27][28][29] and in patients with neurodegenerative disorders associated with cognitive decline [17,19,21,22].…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that depression might significantly impair long-term memory in humans and rodents [ 62 – 64 ]. Previous studies have shown the involvement of various ceramides, their precursors sphingomyelins, and enzymes mediating ceramide synthesis sphingolipid in depression [ 2 , 8 – 10 , 41 , 65 ]. Thus, it may be suggested that the contribution of NC to the mechanism of depression-like behavior might affect long-term memory performance in rats.…”

Section: Discussionmentioning

confidence: 99%

“…One of them, the sphingomyelinase pathway, is based on the enzymes mediating ceramide generation from sphingomyelin, such as acid and neutral sphingomyelinases, and enzymes catalyzing ceramide degradation to sphingosine, such as acid and neutral ceramidases (AC and NC) [2][3][4]. The alterations in the levels and activities of all members of ceramide metabolism are involved in the pathogenesis of psychiatric disorders, such as depression [7][8][9][10], addiction [9,[11][12][13][14][15], as well as neurodegenerative disorders, such as Alzheimer's and Parkinson's disorder [16][17][18][19][20], and other disorders associated with memory loss [21,22].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neutral ceramidase is a marker for cognitive performance in rats and monkeys

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Ceramides are lipid molecules determining cell integrity and intercellular signaling, and thus, involved in the pathogenesis of several psychiatric and neurodegenerative disorders. However, little is known about the role of particular enzymes of the ceramide metabolism in the mechanisms of normal behavioral plasticity. Here, we studied the contribution of neutral ceramidase (NC), one of the main enzymes mediating ceramide degradation, in the mechanisms of learning and memory in rats and non-human primates. Methods Naïve Wistar rats and black tufted-ear marmosets (Callithrix penicillata) were tested in several tests for short- and long-term memory and then divided into groups with various memory performance. The activities of NC and acid ceramidase (AC) were measured in these animals. Additionally, anxiety and depression-like behavior and brain levels of monoamines were assessed in the rats. Results We observed a predictive role of NC activity in the blood serum for superior performance of long-term object memory tasks in both species. A brain area analysis suggested that high NC activity in the ventral mesencephalon (VM) predicts better short-term memory performance in rats. High NC activity in the VM was also associated with worse long-term object memory, which might be mediated by an enhanced depression-like state and a monoaminergic imbalance. Conclusions Altogether, these data suggest a role for NC in short- and long-term memory of various mammalian species. Serum activity of NC may possess a predictive role in the assessing the performance of certain types of memory.

show abstract

Section: Local Nc Activity and Emotional Statussupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neutral ceramidase is a marker for cognitive performance in rats and monkeys

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Supporting this, possibly the activities of both sphingomyelinases and ceramidases were elevated in the brain regions of female rats selectively bred for high versus low anxiety-like behavior. High anxiety rats exhibited increased activity of ASM and neutral sphingomyelinase as well as of acid ceramidase and neutral ceramidase in multiple brain regions associated with anxiety and depressive-like behavior [166]. The functional ASM-ceramide pathway in the rat brain has also been implicated in the extinction of learned behavior-coincided with a reduction of ASM activity and decline of ceramides in dorsal hippocampus-and expression of re-learning-related behavior [167].…”

Section: Major Depression and The Emerging Role Of Asm And Acid Ceramidase In Lysosomal Lipid Turnovermentioning

confidence: 99%

Acid Sphingomyelinase, a Lysosomal and Secretory Phospholipase C, Is Key for Cellular Phospholipid Catabolism

Breiden¹,

Sandhoff

2021

IJMS

View full text Add to dashboard Cite

Here, we present the main features of human acid sphingomyelinase (ASM), its biosynthesis, processing and intracellular trafficking, its structure, its broad substrate specificity, and the proposed mode of action at the surface of the phospholipid substrate carrying intraendolysosomal luminal vesicles. In addition, we discuss the complex regulation of its phospholipid cleaving activity by membrane lipids and lipid-binding proteins. The majority of the literature implies that ASM hydrolyses solely sphingomyelin to generate ceramide and ignores its ability to degrade further substrates. Indeed, more than twenty different phospholipids are cleaved by ASM in vitro, including some minor but functionally important phospholipids such as the growth factor ceramide-1-phosphate and the unique lysosomal lysolipid bis(monoacylglycero)phosphate. The inherited ASM deficiency, Niemann-Pick disease type A and B, impairs mainly, but not only, cellular sphingomyelin catabolism, causing a progressive sphingomyelin accumulation, which furthermore triggers a secondary accumulation of lipids (cholesterol, glucosylceramide, GM2) by inhibiting their turnover in late endosomes and lysosomes. However, ASM appears to be involved in a variety of major cellular functions with a regulatory significance for an increasing number of metabolic disorders. The biochemical characteristics of ASM, their potential effect on cellular lipid turnover, as well as a potential impact on physiological processes will be discussed.

show abstract